This is a prospective randomized placebo-controlled double-blind crossover pilot study determining the effect of dichloroacetate on brain function under clamped hypoglycemia in T1DM.

This study is a prospective randomized placebo-controlled double-blind crossover study designed to address the hypothesis that dichloroacetate has the ability to re-activate brain glucose metabolism under clamped hypoglycemia. The study population is comprised of intensively treated persons with T1D with frequent exposure to hypoglycemia, who have cognitive deficits under hypoglycemia that could be attributed to changes in brain glucose oxidation. The investigators will test the experimental compound DCA in a study that determines whether restoring brain glucose metabolism under hypoglycemia helps maintain cognitive function.

Inclusion Criteria:

T1DM subjects with:

• a history of severe hypoglycemia and/or hypoglycemia unawareness or
• a history of severe hypoglycemia with a blood glucose <54 mg/dL, requiring the assistance of another person (with recovery after the administration of oral carbohydrate, intravenous glucose, or glucagon) or
• at least 2 values <54mg/dl during 2 weeks of CGMS testing during the week prior to study.

Exclusion Criteria:

• Age < 18 years or >55 years.
• Body weight >85 kg at screening visit
• BMI > 30 (female) and >30 (male) kg/m2.
• Untreated proliferative retinopathy
• carriers of glutathione transferase Z1 (GSTZ-1) gene polymorphisms that predispose to DCA accumulation and toxicity

Grouped analysis will be made available after the completion of the study within one year after completion of enrollment at the most.

Beginning 9 months and ending 36 months following article publication.

Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.

For individual participant data meta-analysis